A number of studies suggest that older patients may have reduced or no benefit from the addition of oxaliplatin to fluoropyrimidines as adjuvant chemotherapy for stage III colon cancer (CC).
We ...studied the prognostic impact of age, as well as treatment adherence/toxicity patterns according to age, in patients with stage III CC who received 3 or 6 months of infusional fluorouracil, leucovorin, and oxaliplatin/capecitabine and oxaliplatin (CAPOX) on the basis of data collected from trials from the ACCENT and IDEA databases. Associations between age and time to recurrence (TTR), disease-free survival (DFS), overall survival (OS), survival after recurrence (SAR), and cancer-specific survival (CSS) were assessed by a Cox model or a competing risk model, stratified by studies and adjusted for sex, performance status, T and N stage, and year of enrollment.
A total of 17,909 patients were included; 24% of patients were age older than 70 years (n = 4,340). Patients age ≥70 years had higher rates of early treatment discontinuation. Rates of grade ≥3 adverse events were similar between those older and younger than 70 years, except for diarrhea and neutropenia that were more frequent in older patients treated with CAPOX (14.2%
11.2%;
= .01 and 12.1%
9.6%;
= .04, respectively). In multivariable analysis, TTR was not significantly different between patients <70 years and those ≥70 years, but DFS, OS, SAR, and CSS were significantly shorter in those patients ≥70 years.
In patients ≥70 years with stage III CC fit enough to be enrolled in clinical trials, oxaliplatin-based adjuvant chemotherapy was well tolerated and led to similar TTR compared with younger patients, suggesting similar efficacy. TTR may be a more appropriate end point for efficacy in this patient population.
The bcl-2 proto-oncogene and the p53 tumor suppressor gene are important determinants of tumor cell susceptibility to apoptosis.
bcl-2 and mutant p53 proteins inhibit apoptosis in vitro and can ...provide prognostic information in certain tumor types. We
analyzed bcl-2 and p53 expression in archival pancreatic (n = 35) and ampullary (n = 6) adenocarcinomas, resected for cure,
and their relationship to overall survival. Patients were treated with 5-fluorouracil and irradiation either pre- (n = 21)
or postoperatively (n = 15); 5 patients received surgery alone. Using specific monoclonal antibodies, cytoplasmic bcl-2 and
nuclear p53 proteins were detected in 22 of 40 (55%) and 20 of 37 (54%) tumors, respectively. No relationship was found between
bcl-2 and p53 expression. Neither bcl-2 nor p53 correlated with histological response to preoperative chemoradiation. Lymph
node involvement predicted poor overall survival (P = 0.02). A trend toward improved survival was seen in well-differentiated
(P = 0.08) tumors and in those with increased bcl-2 expression (P = 0.06). p53 expression was not related to clinical outcome.
In a multivariate analysis, nodal status was the single most important predictor of overall survival. Of note, the combined
variable of bcl-2 expression and histological grade was a stronger prognostic variable than nodal status alone. Unlike nodal
status, these features can potentially be evaluated in preoperative biopsy specimens.
Abstract Introduction The aim of this study was to report the physical and functional outcomes after open reduction internal fixation of the olecranon in a large series of patients with region ...specific plating across multiple centers. Patients/Methods Between January 2007 to January 2014, 182 consecutive patients with a displaced olecranon fracture treated with open reduction internal fixation were included in this study. Retrospective review across four trauma centers collected elbow range of motion, DASH scores, hardware complications, and hardware removal. Postoperative visits in the outpatient clinic were at two, six, and twenty-four weeks. After 24 weeks, patients were eligible for hardware removal if symptomatic. All patients were contacted, at least 1 year following surgery, to determine if hardware was removed. Results 182 patients (75 women, 105 men) average age 50 (16–89) with 162 closed and 19 open displaced olecranon fractures were treated with one region specific plate. Nineteen were lost to followup leaving 163 for analysis with all patients united. The most common deficiency was a lack of full extension with 39% lacking at least 10° of extension. Hardware was asymptomatic in 67%, painful upon leaning in 20%, and restricted activities in 11% resulting in a 15% rate of hardware removal. Hardware complaints were more common if a screw was placed in the corner of the plate (P = 0.004). When symptomatic, the area of the plate that was bothersome encompassed the whole plate in 39%, was at the edge of the plate in 33%, and was a screw head in 28%. The DASH scores, collected at final follow-up of 24 weeks, was 10.1 ± 16, indicating moderate disability was still present. Patients who lacked 10° of extension had a DASH of 12.3 as compared with 10.5 for those with near full extension, but this was not significant (P=.5). Conclusion Plating of the olecranon leads to predictable union. The most common complication was lack of full extension with 39% lacking more than 10°, although this did not have any effect on DASH scores. Overall results indicate that disability still exists after 6 months with an average DASH score of 10.
The American Joint Committee on Cancer staging and other prognostic tools fail to account for stage-independent variability in outcome. We developed a prognostic classifier adding Immunoscore to ...clinicopathological and molecular features in patients with stage III colon cancer.
Patient (n = 559) data from the FOLFOX arm of adjuvant trial NCCTG N0147 were used to construct Cox models for predicting disease-free survival (DFS). Variables included age, sex, T stage, positive lymph nodes (+LNs), N stage, performance status, histologic grade, sidedness,
, mismatch repair, and Immunoscore (CD3
, CD8
T-cell densities). After determining optimal functional form (continuous or categorical) and within Cox models, backward selection was performed to analyze all variables as candidate predictors. All statistical tests were two-sided.
Poorer DFS was found for tumors that were T4 vs T3 (hazard ratio HR = 1.76, 95% confidence interval CI = 1.19 to 2.60;
= .004), right- vs left-sided (HR = 1.52, 95% CI = 1.14 to 2.04;
= .005),
(HR = 1.74, 95% CI = 1.26 to 2.40;
< .001), mutant
(HR = 1.66, 95% CI = 1.08 to 2.55;
= .02), and low vs high Immunoscore (HR = 1.69, 95% CI = 1.22 to 2.33;
= .001) (all
<
.02). Increasing numbers of +LNs and lower continuous Immunoscore were associated with poorer DFS that achieved significance (both
s<
.0001). After number of +LNs, T stage, and
, Immunoscore was the most informative predictor of DFS shown multivariately. Among T
N
tumors, Immunoscore was the only variable associated with DFS that achieved statistical significance. A nomogram was generated to determine the likelihood of being recurrence-free at 3 years.
The Immunoscore can enhance the accuracy of survival prediction among patients with stage III colon cancer.
Background.
Preclinical and epidemiological data suggest that metformin might have antineoplastic properties against colon cancer (CC). However, the effect of metformin use on patient survival in ...stage III CC after curative resection is unknown. The survival outcomes were comparable regardless of the duration of metformin use.
Patients and Methods.
Before randomization to FOLFOX (folinic acid, 5‐fluorouracil, oxaliplatin) with or without cetuximab, 1,958 patients with stage III CC enrolled in the N0147 study completed a questionnaire with information on diabetes mellitus (DM) and metformin use. Cox models were used to assess the association between metformin use and disease‐free survival (DFS), overall survival (OS), and the time to recurrence (TTR), adjusting for clinical and/or pathological factors.
Results.
Of the 1,958 patients, 1,691 (86%) reported no history of DM, 115 reported DM with metformin use (6%), and 152 reported DM without metformin use (8%). The adjuvant treatment arms were pooled, because metformin use showed homogeneous effects on outcomes across the two arms. Among the patients with DM (n = 267), DFS (adjusted hazard ratio aHR, 0.90; 95% confidence interval CI, 0.59–1.35; p = .60), OS (aHR, 0.99; 95% CI, 0.65–1.49; p = .95), and TTR (aHR, 0.87; 95% CI, 0.56–1.35; p = .53) were not different for the metformin users compared with the nonusers after adjusting for tumor and patient factors. The survival outcomes were comparable regardless of the duration of metformin use (<1, 1–5, 6–10, ≥11 years) before randomization (ptrend = .64 for DFS, ptrend = .84 for OS, and ptrend = .87 for TTR). No interaction effects were observed between metformin use and KRAS, BRAF mutation status, tumor site, T/N stage, gender, or age.
Conclusions.
Patients with stage III CC undergoing adjuvant chemotherapy who used metformin before the diagnosis of CC experienced DFS, OS, and TTR similar to those for non‐DM patients and DM patients without metformin use.
Implications for Practice:
The present study did not find any relationship between metformin use or its duration and disease‐free survival, time to recurrence, and overall survival in a large cohort of patients with resected stage III colon cancer receiving adjuvant FOLFOX (folinic acid, fluorouracil, oxaliplatin)‐based chemotherapy. This relationship was not modified by KRAS or BRAF mutation or DNA mismatch repair status. Metformin use did not increase or decrease the likelihood of chemotherapy‐related grade 3 or higher adverse events.
Metformin might have antineoplastic properties against colon cancer (CC). Patients with stage III CC enrolled in the N0147 study completed a questionnaire regarding diabetes mellitus (DM) and metformin use. Patients with stage III CC undergoing adjuvant chemotherapy who used metformin before the diagnosis of CC experienced survival outcomes similar to those for non‐DM patients and DM patients without metformin use.
Radiation proctitis is a common complication of abdominal and pelvic radiotherapy; unfortunately, there is no established effective therapy for radiation proctitis. Short-chain fatty acids (SCFA) ...have been effectively used to treat a variety of colitides. We sought to determine whether SCFA enemas have a role in the treatment of radiation proctitis.
Seven patients completed an open-labeled, pilot study to evaluate the effect of SCFA on clinical, endoscopic, and pathological parameters of radiation proctitis.
Four weeks of treatment with SCFA enemas resulted in clinical improvement in all patients. There were modest, but not significant, changes in endoscopic and pathological parameters.
SCFA are a promising therapeutic option in radiation proctitis.
Microsatellite instable/deficient mismatch repair (MSI/dMMR) metastatic colorectal cancers have been reported to have a poor prognosis. Frequent co-occurrence of MSI/dMMR and BRAF
complicates the ...association.
Patients with resected stage III colon cancer (CC) from seven adjuvant studies with available data for disease recurrence and MMR and BRAF
status were analyzed. The primary end point was survival after recurrence (SAR). Associations of markers with SAR were analyzed using Cox proportional hazards models adjusted for age, gender, performance status, T stage, N stage, primary tumor location, grade, KRAS status, and timing of recurrence.
Among 2630 patients with cancer recurrence (1491 men 56.7%, mean age, 58.5 19-85 years), multivariable analysis revealed that patients with MSI/dMMR tumors had significantly longer SAR than did patients with microsatellite stable/proficient MMR tumors (MSS/pMMR) (adjusted hazard ratio aHR, 0.82; 95% CI confidence interval, 0.69-0.98; P = 0.029). This finding remained when looking at patients treated with standard oxaliplatin-based adjuvant chemotherapy regimens only (aHR, 0.76; 95% CI, 0.58-1.00; P = 0.048). Same trends for SAR were observed when analyzing MSI/dMMR versus MSS/pMMR tumor subgroups lacking BRAF
(aHR, 0.84; P = 0.10) or those harboring BRAF
(aHR, 0.88; P = 0.43), without reaching statistical significance. Furthermore, SAR was significantly shorter in tumors with BRAF
versus those lacking this mutation (aHR, 2.06; 95% CI, 1.73-2.46; P < 0.0001), even in the subgroup of MSI/dMMR tumors (aHR, 2.65; 95% CI, 1.67-4.21; P < 0.0001). Other factors associated with a shorter SAR were as follows: older age, male gender, T4/N2, proximal primary tumor location, poorly differentiated adenocarcinoma, and early recurrence.
In stage III CC patients recurring after adjuvant chemotherapy, and before the era of immunotherapy, the MSI/dMMR phenotype was associated with a better SAR compared with MSS/pMMR. BRAF
mutation was a poor prognostic factor for both MSI/dMMR and MSS/pMMR patients.
NCT00079274, NCT00265811, NCT00004931, NCT00004931, NCT00026273, NCT00096278, NCT00112918.
Background: Endoscopic ultrasonography (EUS) is an imaging modality that is now widely used to stage gastrointestinal malignancies. Few studies have addressed the issue of interobserver variability ...in the interpretation of EUS, particularly as it pertains to the staging of rectal carcinoma.
Methods: Twenty-six patients with a diagnosis of rectal carcinoma were evaluated prospectively by three endoscopists. One performed sigmoidoscopy, the second (primary endosonographer) performed an EUS staging examination with full knowledge of the patient history and sigmoidoscopic appearance of the lesion, and the third endoscopist (secondary endosonographer) performed EUS blinded to this information. The results of the respective examinations were then compared.
Results: When the EUS findings of the endosonographers were compared, T stage agreed in 88% of patients, with the following kappa coefficients: T1 (κ = 0.00); T2 (κ = -0.04); T3 (κ = -0.05); T4 (κ = 0.00). Interrator N stage agreed in 73% of patients (κ = 0.42).
Conclusion: Our study prospectively evaluated interobserver variation in staging rectal carcinoma by EUS. The protocol that was followed provides a useful template that eliminated potential observer bias. Fair agreement was demonstrated regarding lymph node assessment. Although the raters agreed in 88% of the patients, kappa statistic analysis did not reach significant agreement, due to this institution's preponderence of UT3 lesions. Thus, validation of our findings in a setting where a broader spectrum of disease is encountered is required. (Gastrointest Endosc 1996;44:573-7.)
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